The cell biological basis of human implantation

doi:10.1053/beog.2000.0116

Best Practice & Research Clinical Obstetrics & Gynaecology

Volume 14, Issue 5, October 2000, Pages 757-764

https://doi.org/10.1053/beog.2000.0116 Get rights and content

Abstract

Understanding the cellular basis of implantation and placental development depends on a combination of the limited morphological evidence in the human with data from other primates, separate studies of pre-implantation embryos and endometrium and in vitro models. There is increasing evidence of a dialogue between embryo and endometrium that begins prior to implantation and evolves rapidly through the successive epithelial and stromal/vascular phases. This includes paracrine signals passing to endometrial tissue from the embryo, and vice versa. The production and timing of these signals by endometrium, and its ability to respond to signals from the blastocyst, are dependent on steroidal sensitization. A complex cascade of cell adhesion mechanisms and local tissue remodelling are required for the establishment of a stable haemochorial interface.

References (60)

P Bouchard et al.
Immunocytochemical localization of oestradiol and progesterone receptors in human endometrium: a tool to assess endometrial maturation
Baillière's Clinical Obstetrics and Gynaecology
(1991)
PA Bergh et al.
The impact of embryonic development and endometrial maturity on the timing of implantation
Fertility and Sterility
(1992)
RW Noyes et al.
Dating the endometrial biopsy
Fertility and Sterility
(1950)
AC Enders
Cytotrophoblast invasion of the endometrium in the human and macaque early villous stage of implantation
Trophoblast Research
(1997)
AC Enders et al.
Comparative placental structure
Advanced Drug Delivery Reviews
(1999)
Lj Vicovac et al.
Trophoblast differentiation during anchoring villus formation in a coculture model of the human implantation site in vitro
Placenta
(1995)
SW Han et al.
Treatment of human endometrial stromal cells with chorionic gonadotropin promotes their morphological and functional differentiation into decidua
Molecular and Cellular Endocrinology
(1999)
JF Schultz et al.
Beta 1- and beta 3-class integrins mediate fibronectin binding activity at the surface of developing mouse peri-implantation blastocysts. Regulation by ligand-induced mobilization of stored receptor
Journal of Biological Chemistry
(1995)
JA Irving et al.
Functional roles of cell surface integrins on human trophoblast cell migration: regulation by TGFβ, IGF-II and IGFBP-1
Experimental Cell Research
(1995)
R Pijnenborg et al.
Trophoblastic invasion of human decidua from 8 to 18 weeks of pregnancy
Placenta
(1980)

ML Iruela-Arispe et al.

Endometrial endothelial cells express estrogen and progesterone receptors and exhibit a tissue specific response to angiogenic growth factors

Microcirculation

(1999)

PA Mote et al.

Colocalization of progesterone receptors A and B by dual immunofluorescent histochemistry in human endometrium during the menstrual cycle

Journal of Clinical Endocrinology and Metabolism

(1999)

MP Snijders et al.

Immunocytochemical analysis of oestrogen receptors and progesterone receptors in the human uterus throughout the menstrual cycle and after the menopause

Journal of Reproduction and Fertility

(1992)

AT Hertig et al.

A description of 34 human ova within the first 17 days of development

American Journal of Anatomy

(1956)

AC Enders

Implantation (embryology)

Encyclopedia of Human Biology.

(1991)

JD Boyd et al.

The Human Placenta

(1970)

M Knoth et al.

Ultrastructure of a human implantation site

Acta Obstetrica et Gynaecologica Scandinavica

(1972)

Lj Vicovac et al.

Epithelial–mesenchymal transition during trophoblast differentiation

Acta Anatomica

(1996)

JD Aplin et al.

Development of cytotrophoblast columns from explanted first trimester placental villi: role of fibronectin and integrin α₅β₁

Biology of Reproduction

(1999)

JD Aplin

Adhesion molecules in implantation

Reviews of Reproduction

(1997)

S Campbell et al.

Cell adhesion molecules on the oocyte and pre-implantation human embryo

Molecular Human Reproduction

(1995)

S Campbell et al.

CD44 is expressed throughout preimplantation human embryo development

Human Reproduction

(1995)

A McLaren et al.

Studies in the transfer of fertilised mouse eggs to uterine foster mothers I: factors affecting the implantation and survival of native and transferred eggs

Journal of Experimental Biology

(1956)

A Psychoyos

Uterine receptivity for nidation

Annals of the New York Academy of Sciences

(1986)

C Sjoblom et al.

Granulocyte–macrophage colony-stimulating factor promotes human blastocyst development in vitro

Human Reproduction

(1999)

AT Fazleabas et al.

Modulation of the baboon uterine endometrium by chorionic gonadotropin during the period of uterine receptivity

Proceedings of the National Academy of Sciences of the USA

(1999)

E Reshef et al.

The presence of gonadotropin receptors in nonpregnant human uterus, human placenta, fetal membranes, and decidua

Journal of Clinical Endocrinology and Metabolism

(1990)

SA Sarani et al.

Morphological evidence for the ‘implantation window’ in human luminal endometrium

Human Reproduction

(1999)

RA Smith et al.

The endometrial cycle: the expression of a secretory component correlated with the luteinizing hormone peak

Human Reproduction

(1989)

Cited by (83)

Expression profile of adhesion molecules in blastocyst vis-a-vis uterine epithelial cells
2021, Theriogenology
Models using in vitro produced buffalo embryos and in vitro cultured uterine epithelial cells (UECs) may be useful in understanding the intricacies of embryo-uterine cross talk. In the present study, buffalo UECs were obtained from slaughterhouse derived non-gravid uterus. UECs monolayer was treated with steroids (10pg/ml estradiol for 24h and 3.14 ng/ml progesterone for another 5 days). In vitro produced buffalo blastocysts were co-cultured over steroid treated UECs monolayer and at 72 h of co-culture, embryo attachment rate was higher in UECs treated with steroids (71.86% vs. 26.55%) while no attachment was observed on plastic surface. Naturally hatched or assisted hatched blastocysts were co-cultured over UECs monolayer treated with 3.14ng/ml progesterone (P4), or without any treatment for 72 h and the effect of co-culture on the expression profile of adhesion related biomolecules was analyed in UECs and blastocysts. Cultured UECs and blastocysts cultured in embryo culture media were considered as control. It was observed that the expression of MUC1 in UECs was significantly (p < 0.05) higher in control group than treatment groups. The relative mRNA abundance of integrins and osteopontin was significantly (p < 0.05) higher in UECs and blastocysts of treatment groups than control group. Expression of IFN-τ was significantly higher (p < 0.05) in embryos co-cultured with UECs than other treatment groups. It can be concluded that P4 supplementation is required for the modulation of adhesion molecules and co-culture of blastocysts and UECs together affect the expression of adhesion molecules both in blastocyts and in UECs.
Cytokine imbalance at materno-embryonic interface as a potential immune mechanism for recurrent pregnancy loss
2021, International Immunopharmacology
Citation Excerpt :
The cytokines that are present at the interface of maternal embryonic units could affect the uterus milieu via the regulation of embryo implantation, growth of placenta, cytotrophoblast production, blood vessel formation, extra-villous trophoblast cell invasion, refashioning of spiral arteries, cell development and apoptosis as well as induction of embryonic tolerance [52,53]. The success of pregnancy essentially depends on reciprocal signaling between the mother and developing blastocyst and decidual receptiveness all through the implantation window [54]. Cytokines along with cell surface receptors are believed to act as communication mediators between trophoblastic and decidual cells [55].
Recurrent pregnancy loss (RPL) is a prominent reproductive disease that distresses about 2%-5% of couples. RPL is the loss of two or more successive spontaneous pregnancies prior to the 20th week of embryo development. The commencement of pregnancy necessitates implantation of the embryo into responsive maternal decidua synchronized with the process of placentation, decidual and myometrial trophoblast incursion as well as refashioning of spiral blood arteries of uterus. The collapse of any of the processes fundamental for pregnancy success may result into an array of pregnancy problems including spontaneous pregnancy loss. Endometrium of human female manufactures an extensive range of cytokines during the proliferative and secretory stage of the menstrual cycle. These endometrial cytokines are thought as major players for making the uterus ready for embryo implantation and placental development during pregnancy. Decidual cytokines regulate the invasion of trophoblast and remodeling of spiral arteries as well as take part in immune suppression to accomplish the pregnancy. Deterrence of maternal rejection of embryo needs a regulated milieu, which takes place essentially at the embryo-maternal interface and the tissues of the uterus. The reasons of RPL remain anonymous in a large number of cases that lead to difficulties in management and severe trauma in couples. Cytokine modulatory therapies have been shown promising for preventing RPL. Further study of novel factors is wanted to establish more effective RPL treatment protocols. The present study aims to review the outcome of cytokine breach at materno-embryonic interface and the efficacy of cytokine modulatory therapies in RPL.
Progress in deciphering trophoblast cell differentiation during human placentation
2020, Current Opinion in Cell Biology
The maintenance of gestational well-being requires the proper development of both the embryo and the placenta. Placental trophoblast cells are the major building blocks of the developing placenta. Abnormal trophoblast differentiation underpins placental-based pregnancy complications. However, the mechanisms that govern trophoblast differentiation remain largely unclear. Recent studies shed light on several proteins and regulators that are involved in governing trophoblast differentiation. The advancement of new tools and novel technologies, such as the human trophoblast stem cell culture system, 3D placental organoids and single-cell multi-omics, has brought incredible insights to the field. Here we review the current literature, paying particular attention to articles published between 2017 and 2019 that have promoted our understanding of human trophoblast cell differentiation and its roles in pregnancy and its complications. At the same time, we address challenges and questions arising in the field of human placental development and disease.
Recurrent implantation failure in IVF: A Canadian Fertility and Andrology Society Clinical Practice Guideline
2020, Reproductive BioMedicine Online
Recurrent implantation failure (RIF) after IVF is a challenging topic for clinicians and can be a devastating reality for some patients with infertility. The purpose of this guideline from the Canadian Fertility and Andrology Society (CFAS) is to provide the most relevant evidence to date for the assessment and management of RIF. This guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. This guideline recognizes the presence of heterogeneity in the definition of RIF. Recommendations are offered here on the investigation of RIF and management options that may increase the chance of a live birth.
Association between estrogen receptor 1 (ESR1) and leukemia inhibitory factor (LIF) polymorphisms can help in the prediction of recurrent implantation failure
2019, Fertility and Sterility
To investigate an association between polymorphisms related to the implantation process that together could help in the prediction of recurrent implantation failure (RIF).
Cohort study.
Private fertility center and reproductive genetics laboratory.
Forty-four women presenting RIF, who were included in study group (RIF group), and two control groups, one with 63 women who were attended at our service and became pregnant after the first IVF/intracytoplasmic sperm injection attempt (control group I) and other with 65 fertile women who had at least two children without any treatment and no history of miscarriage (control group II).
None.
Genotyping was performed in the intron region of TP63, VEGFA, MMP2, ESR1, and ESR2 genes and in the 3′ untranslated region of the LIF gene on genomic DNA using real-time polymerase chain reaction.
The presence of ESR1/AA (rs12199722) and LIF/GT (rs929271) genotypes was more frequent in the RIF group, leading to a 7.9-fold increase in the chance of women presenting with RIF when compared with women who became pregnant on their first cycle of IVF/intracytoplasmic sperm injection and a 2.8-fold increase when compared with women who became pregnant without treatment.
The association between ESR1 and LIF polymorphisms can help in the prediction of RIF.
La asociación entre los polimorfismos del receptor 1 de estrógenos (ESR1) y el factor inhibidor de la leucemia (LIF) puede ayudar en la predicción del fallo recurrente de implantación
Investigar la asociación entre polimorfismos relacionados con el proceso de implantación que, conjuntamente, puedan ayudar en la predicción del Fallo Recurrente de Implantación (RIF).
Estudio de cohortes.
Centro privado de fertilidad y Laboratorio de genética reproductiva.
Cuarenta y cuatro mujeres con RIF que fueron incluidas en el grupo de estudio (grupo RIF) y dos grupos control, uno con 63 mujeres que fueron atendidas en nuestro servicio y quedaron gestantes en el primer ciclo de FIV/inyección intracitoplasmática de espermatozoides (grupo control I), y otro grupo con 65 mujeres fértiles que habían tenido al menos dos hijos sin tratamientos de reproducción y sin historia de abortos (Grupo control II).
Ninguna.
Se realizó genotipado en la región intrónica de los genes TP63, VEGFA, MMP2, ESR1 y ESR2 y en la región 3o no traducida del gen LIF en DNA genómico utilizando reacción en cadena de la polimerasa en tiempo-real.
La presencia de los genotipos ESR1/AA (rs12199722) y LIF/GT (rs929271) fue más frecuente en el grupo con RIF, llevando a un incremento de 7,9 veces en la probabilidad de presentar aborto cuando se compararon con las mujeres que consiguieron el embarazo en su primer ciclo de FIV/ICSI y a una probabilidad 2.8 veces mayor cuando se compararon con mujeres que quedaron gestantes sin tratamiento.
La asociación entre los polimorfismos ESR1 y LIF puede ayudar en la predicción de RIF.
The molecular signature of the endometrial receptivity: Research and clinical application
2018, Reproductomics: The -Omics Revolution and Its Impact on Human Reproductive Medicine
In this chapter, we will cover the basics of the human endometrial physiology, structure, and functionality, through specifically focusing on the endometrial receptivity acquisition and the molecular signature involving this process. The history related to endometrial characterization from morphological, histological, and ultrasound visualization to the molecular characterization and the omics revolution will be reviewed. Furthermore, we will summarize the literature in relation to different types of molecules, that is, transcripts, proteins, and metabolites. We will also discuss their use for research and their clinical application, with special attention to those already commercialized as diagnostic tools. Finally, we will highlight new opportunities in the field of noninvasive omics for the assessment of endometrial receptivity, by using endometrial fluid as an alternative for the disruptive biopsy procedure.

View all citing articles on Scopus

^f1: Address for correspondence: Research Floor, St Mary's Hospital, Manchester M13 0JH, UK.

View full text

Regular ArticleThe cell biological basis of human implantation

Abstract

Baillière's Clinical Obstetrics and Gynaecology

Fertility and Sterility

Fertility and Sterility

Trophoblast Research

Advanced Drug Delivery Reviews

Placenta

Molecular and Cellular Endocrinology

Journal of Biological Chemistry

Experimental Cell Research

Placenta

Endometrial endothelial cells express estrogen and progesterone receptors and exhibit a tissue specific response to angiogenic growth factors

Microcirculation

Colocalization of progesterone receptors A and B by dual immunofluorescent histochemistry in human endometrium during the menstrual cycle

Journal of Clinical Endocrinology and Metabolism

Immunocytochemical analysis of oestrogen receptors and progesterone receptors in the human uterus throughout the menstrual cycle and after the menopause

Journal of Reproduction and Fertility

A description of 34 human ova within the first 17 days of development

American Journal of Anatomy

Implantation (embryology)

Encyclopedia of Human Biology.

The Human Placenta

Ultrastructure of a human implantation site

Acta Obstetrica et Gynaecologica Scandinavica

Epithelial–mesenchymal transition during trophoblast differentiation

Acta Anatomica

Development of cytotrophoblast columns from explanted first trimester placental villi: role of fibronectin and integrin α5β1

Biology of Reproduction

Adhesion molecules in implantation

Reviews of Reproduction

Cell adhesion molecules on the oocyte and pre-implantation human embryo

Molecular Human Reproduction

CD44 is expressed throughout preimplantation human embryo development

Human Reproduction

Studies in the transfer of fertilised mouse eggs to uterine foster mothers I: factors affecting the implantation and survival of native and transferred eggs

Journal of Experimental Biology

Uterine receptivity for nidation

Annals of the New York Academy of Sciences

Granulocyte–macrophage colony-stimulating factor promotes human blastocyst development in vitro

Human Reproduction

Modulation of the baboon uterine endometrium by chorionic gonadotropin during the period of uterine receptivity

Proceedings of the National Academy of Sciences of the USA

The presence of gonadotropin receptors in nonpregnant human uterus, human placenta, fetal membranes, and decidua

Journal of Clinical Endocrinology and Metabolism

Morphological evidence for the ‘implantation window’ in human luminal endometrium

Human Reproduction

The endometrial cycle: the expression of a secretory component correlated with the luteinizing hormone peak

Human Reproduction

Regular Article
The cell biological basis of human implantation

Development of cytotrophoblast columns from explanted first trimester placental villi: role of fibronectin and integrin α₅β₁